CELL RESPONSE AND REGULATION PROGRAM ABSTRACT The Cell Response and Regulation (CRR) Program is a laboratory-based basic science program focused on deciphering cellular mechanisms involved in cancer. CRR's experimental approaches range from biochemistry to work with patient tissues. CRR discovery science supports Huntsman Cancer Institute's focus on genetics and individualized oncology by providing insights into cancer pathways that serve as new foundations to address critical clinical issues. CRR members' basic discoveries are highly relevant to the areas of cancer prevention, target identification, biomarker development, prognostics, diagnostics, and therapy. CRR Research focuses on mechanisms important in 1) regulation of cell turnover; 2) aberrant signaling in cancer and drug resistance; and 3) cell adhesion, cell migration, and metastasis. A major asset of the Program is the development of robust preclinical models of cancer, including zebrafish models of neural crest- derived tumors and mouse models of breast, lung, pancreatic, brain, and skin cancers, in which tumors are induced de novo in a physiologic context. CRR members also collaborate with clinical colleagues to develop xenograft models that faithfully recapitulate the histology and biologic behavior of patient-derived cancers. Major achievements in this funding period include improved understanding of the machinery that executes cell division, elucidation of signaling pathways involved in epithelial homeostasis and migration, and identification of a new biomarker for breast cancer, a critical mediator of drug resistance in myeloma, and factors that drive brain tumor and melanoma metastasis. Basic CRR discoveries are leading to early phase clinical trials in breast cancer and melanoma and have impacted a chemoprevention trial in colon cancer. Co-Led by Douglas Grossman, MD, PhD, and Katharine Ullman, PhD, CRR has 26 members from 12 University of Utah departments in three colleges, including five new members who were strategically recruited. Notably, 27% of CRR members are either MD/PhDs or MDs, bringing added clinical perspective. In 2013, CRR members had $9.8M in annual total funding for cancer research projects, including 34% from NCI (tripled from 11% in 2008). Since July 2009, 16 new collaborative grants were obtained, and CRR research was reported in 212 publications (18% intra- and 37% inter-programmatic collaborations). All full members (100%) have peer-reviewed funding, and many have received distinguished awards. The Cancer Center enhances the Program's goals by providing state-of-the-art facilities, Shared Resources, programmatic funds, and support for recruitments. Over the next five years, the CRR Program will continue to foster synergistic cancer-focused research by facilitating productive interactions between scientists and clinicians, and to cultivate CRR-based research discoveries with potential for clinical application.